Migraine + Anti-emetic

Question 1

What are the four components of migraine syndrome?

Answer 1

PRODROME
= vague changes in mood, appetite

AURA
= neurological disturbances

HEADACHE

RESOLUTION

Question 2

Characterize a migraine headache

Answer 2

Throbbing

Usually one-sided

N/V, gastric stasis, photophobia, and/or phonophobia

Question 3

What is the neurovascular theory?

Answer 3

Abnormal neural activation

Leads to…
Vasodilation, local inflammation
= MIGRAINE!

Question 4

What is cortical spreading depression (CSD)?

Answer 4

Wave of strong depolarization that spreads slowly over the cortical surface

Followed by prolonged depression

Question 5

What happens following CSD cording to neurovascular theory for migraine?

Answer 5

CSD in cortex leads to release of K+, H+, NO and PGs into interstitial fluid.

These mediators cross meningeal blood vessel and stimulate nerve endings

Substance P and CGRP are released and can lead to release of inflammatory mediators from mast cells, and plasma extravasation

Question 6

What class of drugs are very effective against migraine,

Decreasing release of
Substance P
CGRP
Vasoconstriction

Answer 6

5-HT agonists

1B and 1D

Question 7

What are general therapies for acute migraine?

Answer 7

NSAIDs (+/- caffeine)

Antiemetics
+Metoclopramide

Opioid analgesics = last resort!

Question 8

What are specific therapies for acute migraine?

Answer 8

5-HT (1B/1D) agonists
= “triptans”
= sumatriptan

Ergo Alkaloids
= Ergotamine, Dihydroergotamine

Question 9

What are adverse effects of “triptans”?

Answer 9

Paresthesias, flushing, fatigue, dizziness, nausea

Heavy/tightness in chest

Peripheral vasoconstriction + vasospasm

Question 10

What are CIs for “triptans”?

Answer 10

CAD

Cerebrovascular disease

PVD

Uncontrolled HTN

Question 11

What are DDIs associated with “triptans”?

Answer 11

Metabolized by MAO
- MAO inhibitors

Used in caution with patients taking SSRIs or SNRIs to avoid serotonin syndrome

Question 12

What AEs are associated with ergot alkaloids?

Answer 12

N/V

Can cause fetal distress and uterine contractions

Fibrotic thickening of cardiac valves

Peripheral vasoconstriction ‼️‼️

Question 13

What are symptoms of ergot poisoning?

Answer 13

Vascular occlusion

limb ischemia

Gangrene

Question 14

What are CIs associated with ergot alkaloids?

Answer 14

CAD

PVD

Uncontrolled HTN

Pregnancy

Question 15

What are prophylactic agents for migraine?

Answer 15

1st line =
+beta antagonists (propranolol, timolol, metoprolol)
+antiepileptic drugs (valproic acid, divalproex, topiramate)
+antidepressants (amitriptyline, venlafaxine)

ACEIs, ARBs (lisinopril, candesartan)
CCBs (verapamil)
Muscle relaxants (Botox)

Question 16

What are alternative therapies for prevention of migraine?

Answer 16

Butterbur extract
**best evidence

CoQ10
Feverfew
Riboflavin
Mg
Melatonin

Question 17

What receptors when stimulated involve N/V?

Answer 17

5HT3
D2

mAChR
H1

NK1

Question 18

What inputs contribute to the vomiting response?

Answer 18

Chemoreceptor trigger zone (CTZ) = 5HT3, D2, opioid, NK1(?)

Vestibular apparatus =mAChR, H1

Higher centers = odor, tastes, fear

Stomach Small intestine = 5HT3

Pharynx = gagging

Question 19

What are causes of 5HT3 mediated emetic effects?

Answer 19

CINV

Radiation

Acute gastroenteritis

Aspirin, ferrous sulfate, other drugs

Surgery

(Serotonin released by intestinal irritants)

Question 20

What are examples of 5HT3 antagonists?

Answer 20

“Setrons”

Question 21

What are AEs associated with 5HT3 antagonists?

Answer 21

Mild headache/dizziness
Constipation

All (except palonosetron) can inc. QT interval

Question 22

What are indications for 5HT3 antagonists?

Answer 22

Acute CINV
(Enhanced with NK1 antagonist and corticosteroid)

RINV

PONV

Acute gastroenteritis induced NV

Question 23

What are examples of DA agonists?

How do they contribute to emetic effects?

Answer 23

Can induce NV by stimulating D2 receptors in CTZ

Ropinirole
Pramipexole
Rotigotine

Question 24

What are examples of D2 ANTAgonists ???

Answer 24

Proclorperazine

Chlorpromazine

Metoclopramide

Question 25

What can D2 antagonists for antiemetic effects lead to?

Answer 25

Can cause EPS
(Motor symptoms from dopamine blockade)

Diphenhydramine can be administered to prevent or attenuate acute dystonia when agents given parenterally at high doses

Question 26

What is the black box warning associated with a D2 antagonist antiemetic agent?

Answer 26

Metoclopramide

Chronic use => tardive dyskinesia

Question 27

What are indications for phenothiazines and metoclopramide?

Answer 27

Phenothiazines
=general purpose (not CINV)

Metoclopramide
\+PONV
\+migraine-induced NV
\+GI motility disorders
\+CINV

Question 28

What mAChR antagonist is used for antiemetic effects?

Answer 28

Scopolamine

Question 29

What AEs and CIs are associated with scopolamine?

Answer 29

AEs

• Xerostomia
• constipation
• urinary retention
• drowsiness
• visual disturbances

CIs/cautions:

• glaucoma
• GI, urinary tract obstruction
• BPH

Question 30

What H1 antihistamines are used as antiemetic agents?

Answer 30

Diphenhydramine

Dimenhydrinate

Meclizine

Question 31

What are examples of NK1 receptor antagonists used as antiemetic agents?

Answer 31

“Pitants”

Aprepitant

Netupitant

Rolapitant

Question 32

What are indications for NK1 receptor antagonists?

Answer 32

CINV

PONV = aprepitant

Question 33

What corticosteroid is used as an antiemetic?

What are the indications?

Answer 33

Dexamethasone

CINV
PONV

Question 34

What cannabinoids are used for antiemetic function?

What are the indications and AEs?

Answer 34

Dronabinol
Nabilone

indication: CINV

AEs:

• euphoria/dysphoria
• vertigo
• paranoia
• inc. appetite

Question 35

When are benzodiazepines used as antiemetics?

Answer 35

Weak antiemetic effects used as adjunct to prevent CINV and PONV